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Nevin Manimala Statistics

Isolated Kratom Use Disorder Treated with Extended-Release Buprenorphine Taper

J Addict Med. 2024 May 22. doi: 10.1097/ADM.0000000000001328. Online ahead of print.

ABSTRACT

This case report highlights a 36-year-old male without history of psychiatric disease, chronic pain, or substance use disorder who developed severe substance use disorder per Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria to kratom. He was successfully treated with sublingual buprenorphine after a 3-year period of intermittent withdrawal management and trials of oral and extended-release injectable naltrexone. After a period of abstinence from kratom, he was tapered from buprenorphine using 2 monthly injections of 100 mg extended-release buprenorphine. His case underscores some of the current uncertainties around kratom use disorder diagnosis and treatment.

PMID:38776432 | DOI:10.1097/ADM.0000000000001328

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Nevin Manimala Statistics

Benzodiazepine Discharge Prescriptions from Emergency Departments across the United States between 2012 and 2019: A National Analysis

J Addict Med. 2024 May 22. doi: 10.1097/ADM.0000000000001310. Online ahead of print.

ABSTRACT

OBJECTIVES: Benzodiazepines are commonly misused medications frequently implicated in overdose deaths. Data show that benzodiazepine prescribing is associated with increased misuse. We sought to determine national trends in benzodiazepine prescribing from the emergency department (ED).

METHODS: This is a retrospective review of the National Hospital Ambulatory Medical Care Survey from 2012 to 2019. Our primary outcome was to evaluate trends in ED visits where a benzodiazepine was prescribed at discharge. Secondarily, we identified commonly prescribed benzodiazepines and assessed trends over time. We examined demographic data and used descriptive statistics and Spearman rho or Pearson correlation coefficient as applicable.

RESULTS: Between 2012 and 2019, there were 13,848,578 visits where benzodiazepines were prescribed at ED discharge. In 2012 and 2019, there were 1,407,478 visits (1.1% of all ED visits) and 1,361,372 visits (0.9%), respectively, where benzodiazepines were prescribed (mean [SD], 1,731,072 [287,623] [1.26%]), with no trend (P = 0.31). Common benzodiazepines prescribed were diazepam (5,980,279 visits, 43.2% of all prescriptions), alprazolam (3,306,549, 23.9%), and clonazepam (2,105,963, 15.2%), with no changes over time. Fifteen percent of prescriptions were for patients 65 years or older.

CONCLUSION: Despite reports of increased misuse, there was no change in ED discharge benzodiazepine prescribing. Concerningly, alprazolam, a benzodiazepine with high misuse potential, was frequently prescribed despite limited ED indications, and there was a large percentage of visits where benzodiazepines were prescribed to older adults despite warnings for adverse effects in this population. Future studies should assess rational prescribing and the role of targeted interventions to curb inappropriate use.

PMID:38776422 | DOI:10.1097/ADM.0000000000001310

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Nevin Manimala Statistics

Association of ambulance diversion policy on EMS transport and ambulance patient offload times: A comparison of three strategies

Prehosp Emerg Care. 2024 May 22:1-7. doi: 10.1080/10903127.2024.2359505. Online ahead of print.

ABSTRACT

Objectives: Despite limited supporting data, hospitals continue to apply ambulance diversion (AD). Thus, we examined the impact of three different diversion policies on diversion hours, transport time (TT; leaving scene to arrival at the hospital), and ambulance patient offload time (APOT; arrival at the hospital to patient turnover to hospital staff) for 9-1-1 transports in a 22-hospital county Emergency Medical Services (EMS) system.Methods: This retrospective study evaluated metrics during periods of three AD policies, each 27 days long: hospital-initiated (Period 1), complete suspension (Period 2), and County EMS-initiated (Period 3). We described the median transports and diversion hours, and compared the daily average and daily 90th percentile TT and APOT during the three study periods.Results: Over the study period, there were 50,992 total transports in the county; Period 3 had fewer median transports per day than Period 1 (581 vs 623, p < 0.001), while Period 2 was similar to Period 1 (606 vs 623, p = 0.108). Median average daily diversion hours decreased from 98.1 hours during Period 1 to zero hours during both Periods 2 (p < 0.001) and 3 (p < 0.001). Median daily average TT decreased from 18.3 minutes in Period 1 to 16.9 minutes in both Periods 2 (p < 0.001) and 3 (p < 0.001). Median daily 90th percentile TT showed a similar decrease from 30.2 minutes in Period 1 to 27.5 in Period 2 (p < 0.001), and to 28.1 in Period 3 (p = 0.001). Median average daily APOT was 26.0 minutes during Period 1, similar at 25.2 minutes during Period 2 (p = 826) and decreased to 20.4 minutes during Period 3 (p < 0.001). The median daily 90th percentile APOT was 53.9 minutes during Period 1, similar at 51.7 minutes during Period 2 (p = 0.553) and decreased to 40.3 minutes during Period 3 (p < 0.001).Conclusions: Compared to hospital-initiated AD, enacting no AD or County EMS-initiated AD was associated with less diversion time; TT and APOT showed statistically significant improvement without hospital-initiated AD but were of unclear clinical significance. EMS-initiated AD was difficult to interpret as that period had significantly fewer transports. EMS systems should consider these findings when developing strategies to improve TT, APOT, and system use of diversion.

PMID:38776421 | DOI:10.1080/10903127.2024.2359505

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Nevin Manimala Statistics

Integrated analysis of blood DNA methylation, genetic variants, circulating proteins, microRNAs, and kidney failure in type 1 diabetes

Sci Transl Med. 2024 May 22;16(748):eadj3385. doi: 10.1126/scitranslmed.adj3385. Epub 2024 May 22.

ABSTRACT

Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5′-cytosine-phosphate-guanine-3′ loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at P = 6.62 × 10-14. In conclusion, our multiomics study provides insights into mechanisms through which variation of DNAmet may affect KF development and shows that blood cell DNAmet at certain CpGs can improve risk prediction for KF in T1D.

PMID:38776390 | DOI:10.1126/scitranslmed.adj3385

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Nevin Manimala Statistics

Wearable robots for the real world need vision

Sci Robot. 2024 May 22;9(90):eadj8812. doi: 10.1126/scirobotics.adj8812. Epub 2024 May 22.

ABSTRACT

To enhance wearable robots, understanding user intent and environmental perception with novel vision approaches is needed.

PMID:38776377 | DOI:10.1126/scirobotics.adj8812

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Nevin Manimala Statistics

On the role of native contact cooperativity in protein folding

Proc Natl Acad Sci U S A. 2024 May 28;121(22):e2319249121. doi: 10.1073/pnas.2319249121. Epub 2024 May 22.

ABSTRACT

The consistency of energy landscape theory predictions with available experimental data, as well as direct evidence from molecular simulations, have shown that protein folding mechanisms are largely determined by the contacts present in the native structure. As expected, native contacts are generally energetically favorable. However, there are usually at least as many energetically favorable nonnative pairs owing to the greater number of possible nonnative interactions. This apparent frustration must therefore be reduced by the greater cooperativity of native interactions. In this work, we analyze the statistics of contacts in the unbiased all-atom folding trajectories obtained by Shaw and coworkers, focusing on the unfolded state. By computing mutual cooperativities between contacts formed in the unfolded state, we show that native contacts form the most cooperative pairs, while cooperativities among nonnative or between native and nonnative contacts are typically much less favorable or even anticooperative. Furthermore, we show that the largest network of cooperative interactions observed in the unfolded state consists mainly of native contacts, suggesting that this set of mutually reinforcing interactions has evolved to stabilize the native state.

PMID:38776371 | DOI:10.1073/pnas.2319249121

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Nevin Manimala Statistics

Genome-wide discovery of InDels and validation of PCR-Based InDel markers for earliness in a RIL population and genotypes of lentil (Lens culinaris Medik.)

PLoS One. 2024 May 22;19(5):e0302870. doi: 10.1371/journal.pone.0302870. eCollection 2024.

ABSTRACT

The systematic identification of insertion/deletion (InDel) length polymorphisms from the entire lentil genome can be used to map the quantitative trait loci (QTL) and also for the marker-assisted selection (MAS) for various linked traits. The InDels were identified by comparing the whole-genome resequencing (WGRS) data of two extreme bulks (early- and late-flowering bulk) and a parental genotype (Globe Mutant) of lentil. The bulks were made by pooling 20 extreme recombinant inbred lines (RILs) each, derived by crossing Globe Mutant (late flowering parent) with L4775 (early flowering parent). Finally, 734,716 novel InDels were identified, which is nearly one InDel per 5,096 bp of lentil genome. Furthermore, 74.94% of InDels were within the intergenic region and 99.45% displayed modifier effects. Of these, 15,732 had insertions or deletions of 20 bp or more, making them amenable to the development of PCR-based markers. An InDel marker I-SP-356.6 (chr. 3; position 356,687,623; positioned 174.5 Kb from the LcFRI gene) was identified as having a phenotypic variance explained (PVE) value of 47.7% for earliness when validated in a RIL population. Thus, I-SP-356.6 marker can be deployed in MAS to facilitate the transfer of the earliness trait to other elite late-maturing cultivars. Two InDel markers viz., I-SP-356.6 and I-SP-383.9 (chr. 3; linked to LcELF3a gene) when tested in 9 lentil genotypes differing for maturity duration, clearly distinguished three early (L4775, ILL7663, Precoz) and four late genotypes (Globe Mutant, MFX, L4602, L830). However, these InDels could not be validated in two genotypes (L4717, L4727), suggesting either absence of polymorphism and/or presence of other loci causing earliness. The identified InDel markers can act as valuable tools for MAS for the development of early maturing lentil varieties.

PMID:38776345 | DOI:10.1371/journal.pone.0302870

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Nevin Manimala Statistics

Incidence of lost to follow up among HIV-positive children on antiretroviral therapy in Ethiopia: Systematic review and meta-analysis

PLoS One. 2024 May 22;19(5):e0304239. doi: 10.1371/journal.pone.0304239. eCollection 2024.

ABSTRACT

BACKGROUND: At the end of 2022, globally, only 46% of children (aged 0-14 years) on ART had suppressed viral loads. Viral load suppression is crucial to reduce HIV-related deaths. To suppress the viral load at the expected level, children must be retained in ART treatment. Nevertheless, lost to follow-up from ART treatment continues to be a global challenge, particularly, in developing countries. Previously, primary studies were conducted in Ethiopia to assess the incidence of lost to follow-up among HIV-positive children on ART treatment. However, variations have been seen among the studies. Therefore, this systematic review and meta-analysis aimed to estimate the pooled incidence of lost to follow-up among HIV-positive children on ART and identify its associated factors in Ethiopia.

METHODS: We searched PubMed, HINARI, Science Direct, Google Scholar, and African Journals Online to obtain articles published up to November 20, 2023. Critical appraisal was done using the Joanna Briggs Institute checklist. Heterogeneity was identified using I-square statistics. Funnel plot and Egger’s tests were used to identify publication bias. Data was presented using forest plots and tables. Random and fixed-effect models were used to compute the pooled estimate.

RESULTS: Twenty-four studies were included in the final analysis. The pooled incidence of lost to follow-up among HIV-positive children on ART was 2.79 (95% CI: 1.99, 3.91) per 100-child-year observations. Advanced HIV disease (HR: 2.20, 95% CI: 1.71, 2.73), having opportunistic infection (HR: 2.59, 95% CI: 1.39; 4.78), fair or poor ART treatment adherence (HR: 2.92, 95% CI: 1.31; 6.54) and children aged between 1-5 years (HR: 2.1,95% CI: 1.44; 2.95) were factors associated with lost to follow up among HIV positive children on ART.

CONCLUSIONS: The overall pooled incidence of lost to follow-up among HIV-positive children on ART is low in Ethiopia. Therefore, counseling on ART drug adherence should be strengthened. Moreover, emphasis has to be given to children with advanced HIV stage and opportunistic infection to reduce the rate of lost to follow up among HIV-positive children on ART.

TRIAL REGISTRATION: Registered in PROSPERO with ID: CRD42024501071.

PMID:38776343 | DOI:10.1371/journal.pone.0304239

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Nevin Manimala Statistics

Prevalence and causes of blindness and visual impairment in Kogi state, Nigeria-Findings from a Rapid assessment of avoidable blindness survey

PLoS One. 2024 May 22;19(5):e0294371. doi: 10.1371/journal.pone.0294371. eCollection 2024.

ABSTRACT

PURPOSE: To determine the prevalence and causes of blindness and visual impairment among adults in Kogi, Nigeria.

METHODS: A Rapid assessment of avoidable blindness (RAAB) protocol was used with additional tools measuring disability and household wealth to measure the prevalence of blindness and visual impairment (VI) and associations with sex, disability, wealth, cataract surgical coverage and its effectiveness.

RESULTS: Age- and sex-adjusted all-cause prevalence of bilateral blindness was 3.6% (95%CI 3.0-4.2%), prevalence of blindness among people living with additional, non-visual disabilities was 38.3% (95% CI 29.0-48.6%) compared to 1.6% (95%CI 1.2-2.1%; [Formula: see text] = 771.9, p<0.001) among people without additional disabilities. Cataract was the principal cause of bilateral blindness (55.3%). Cataract surgical coverage (CSC) at visual acuity (VA) 3/60 was 48.0%, higher among men than women (53.7% vs 40.3%); 12.0% among people with non-visual disabilities; 66.9% among people without non-visual disabilities, being higher among people in the wealthiest two quintiles (41.1%) compared to the lowest three (24.3%). Effective Cataract Surgical Coverage at Visual Acuity 6/60 was 31.0%, higher among males (34.9%) than females (25.5%), low among people with additional, non-visual disabilities (1.9%) compared to people with no additional disabilities (46.2%). Effective CDC was higher among people in the wealthiest two quintiles (411%) compared to the poorest three (24.3%). Good surgical outcome (VA>6/18) was seen in 61 eyes (52.6%) increasing to 71 (61.2%) eyes with best correction. Cost was identified as the main barrier to surgery.

CONCLUSION: Findings suggest there exists inequalities in eye care with women, poorer people and people with disabilities having a lower Cataract Surgical Coverage, thereby, underscoring the importance of eye care programs to address these inequalities.

PMID:38776330 | DOI:10.1371/journal.pone.0294371

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Nevin Manimala Statistics

The in vitro assessment of rheological properties and dentin remineralization of saliva substitutes containing propolis and aloe vera extracts

PLoS One. 2024 May 22;19(5):e0304156. doi: 10.1371/journal.pone.0304156. eCollection 2024.

ABSTRACT

Saliva substitutes with enhanced dentin remineralization properties were expected to help manage caries progression in patients with xerostomia. This in vitro study examined the rheological properties and remineralization action of experimental saliva substitutes containing propolis extract and aloe vera extract on demineralized dentin. Four experimental saliva substitutes were formulated with varying concentrations of propolis extract (P) and aloe vera extract (A) were prepared. A commercial saliva substitute (Biotene Oral Rinse) was used as a commercial comparison. The rheological properties and viscosity of these materials were measured using a strain-controlled rheometer (n = 3). The remineralizing actions of saliva substitutes on demineralized dentin after 2 weeks were determined using ATR-FTIR and SEM-EDX (n = 8). The results were expressed as a percentage increase in the mineral-to-matrix ratio. Biotene demonstrated a significantly higher viscosity (13.5 mPa·s) than experimental saliva substitutes (p<0.05). The addition of extracts increased the viscosity of the saliva substitutes from 4.7 mPa·s to 5.2 mPa·s. All formulations showed minimal shear thinning behavior, which was the viscoelastic properties of natural saliva. The formulation containing 5 wt% of propolis exhibited the highest increase in the median mineral-to-matrix ratio (25.48%). The SEM-EDX analysis revealed substantial mineral precipitation in demineralized dentin, especially in formulations with 5 wt% or 2.5 wt% of propolis. The effect of the aloe vera extract was minimal. The addition of propolis and aloe vera extracts increased the viscosity of saliva substitutes. the addition of propolis for 2.5 or 5 wt% to saliva substitutes increased mineral apatite precipitation and tubule occlusion. To conclude, the saliva substitute containing propolis extract demonstrated superior remineralizing actions compared with those containing only aloe vera extract.

PMID:38776324 | DOI:10.1371/journal.pone.0304156